The overall aims of this proposal are to conduct phase Il studies of novel agents in patients with gynecologic malignancies through a multiinsitutional consortium based in New York, the New York Gynecologic Oncology Group (NY GOG). Specifically this proposal will focus on trials of combinations of novel retinoids (R) + interferon (IFN) in patients with locally advanced or advanced cervix cancer and on topoisomerase-I inhibitors in patients with refractory ovarian carcinoma with the goal of identifying active regimens and characterizing the toxicities of these regimens. The NY GOG is well-suited to carry out such studies because of: the close collaboration between Gynecologic Oncologists, Medical Oncologists, Radiation Oncologists, and affiliated laboratory scientists; the large population base with both cervical and ovarian cancers served by this Consortium; and a previous track-record of rapid accrual to such studies. The NY GOG will carry out 2-3 phase II studies per year. The NY GOG is currently performing a laboratory-based phase Il trial of all-trans retinoic acid (RA) + IFN in patients with advanced cervix cancer which will serve as a model for the phase Il studies of R + IFN, and New York University (NYU) is currently performing phase Il trials of novel schedules of topo-l inhibitors which will be models for the proposed trials in ovarian cancer. Four laboratory subprojects will provide correlative information which will be useful in guiding the further development of these therapies. In subproject 1, polymerase chain reaction technology will be employed to detect and type human papillomavirus (HPV) in biopsy specimens from patients treated with R + IFN. In subproject 2, pharmacokinetic studies will be performed to measure levels of R both acutely and chronically. In subproject 3, levels of mRNA for retinoic acid receptors (RARalpha, -beta, -gamma, and RXR) and cytoplasmic retinoic acid binding proteins (CRABP l and II) will be measured in biopsy specimens. In subproject 4, levels of topo-l will be assayed in ovarian tissue by Western blot. The results of these laboratory assays will be correlated with response to therapy, response duration, and clinical outcome of patients entered on these trials with the goals of determining subpopulations of patients likely to benefit from treatment with these combinations and to guide development of future regimens.